The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2023 Jun 28

PMID 37376543

Authors

Clairine I S Larsen

Kinjal Majumder

Affiliations

Soon will be listed here.

Abstract

Minute Virus of Mice (MVM) is an autonomous parvovirus of the family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 localization to cellular DDR sites is independent of ATM or DNA-PK signaling but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.

Citing Articles

Development of a Double-Antibody Sandwich ELISA Based on a Monoclonal Antibody against the Viral NS1 Protein for the Detection of Chicken Parvovirus.

Zhang M, Liao J, Xie Z, Zhang Y, Luo S, Li M Pathogens. 2024; 13(3).

PMID: 38535564 PMC: 10976255. DOI: 10.3390/pathogens13030221.

For better or worse: crosstalk of parvovirus and host DNA damage response.

Chen S, Liu F, Yang A, Shang K Front Immunol. 2024; 15:1324531.

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